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Query: CAS:189388-22-5 (Endomorphin-1)
 112 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Two highly-selective mu-opioid receptor agonists, endomorphin-1 and -2, were recently purified from bovine brain and are postulated to be endogenous mu-opioid receptor ligands. We sought to determine the effects of these ligands at the spinal level in mice. Endomorphin-1 and -2 produced short acting, naloxone-sensitive antinociception in the tail flick test and inhibited the behavior elicited by intrathecally injected substance P. Both endomorphin-1 and -2 were anti-allodynic in the dynorphin-induced allodynia model. Although acute tolerance against both endomorphins developed rapidly, endomorphin-1 required a longer pretreatment time before tolerance was observed. We conclude that the endomorphins are potent spinal antinociceptive and anti-allodynic agents and that they or related compounds may prove therapeutically useful as spinal analgesics.
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PMID:Spinal analgesic actions of the new endogenous opioid peptides endomorphin-1 and -2. 933 28

Endomorphin 1 and 2 are recently discovered endogenous ligands for the mu-opioid receptor. In the present study, responses to intravenous administration of endomorphin 1 and 2 were investigated in the systemic vascular bed of the rat. Endomorphin 1 and 2 induced dose-related decreases in systemic arterial pressure when injected in doses of 10-100 nmol/kg i.v.. The decreases in systemic arterial pressure in response to endomorphin 1 and 2 were associated with significant decreases in heart rate, cardiac output, and total peripheral resistance. The endogenous ligand for the ORL1 receptor, nociceptin/OFQ had similar effects on systemic arterial pressure, heart rate, cardiac output, and total peripheral resistance in the rat. Injections of isoproterenol (1 microgram/kg i.v.) and calcitonin gene-related peptide (CGRP; 0.3 nmol/kg i.v.), decreased systemic arterial pressure and total peripheral resistance. However these decreases in arterial pressure were associated with increases in heart rate and cardiac output. The results of the present study demonstrate that the endomorphin peptides have significant vasodilator activity in the systemic vascular bed of the rat and show that this response is associated with a decrease in heart rate and cardiac output.
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PMID:Endomorphin 1 and 2, endogenous ligands for the mu-opioid receptor, decrease cardiac output, and total peripheral resistance in the rat. 939 42

Endomorphin 1 and endomorphin 2 are newly-discovered endogenous ligands for the mu-opioid receptor. In the present study, responses to intra-arterial injections of endomorphin 1 and 2 were investigated in the hindquarters vascular bed of the rat. Under constant-flow conditions, endomorphin 1 and 2 induced dose-dependent decreases in hindquarters perfusion pressure when injected in doses of 3-100 nmol into the hindquarters perfusion circuit. Vasodilator responses to endomorphin 1 and 2 and met-enkephalin were attenuated by the opioid receptor antagonist naloxone (2 mg/kg i.v.) at a time when vasodilator responses to isoproterenol were not altered. In terms of relative vasodilator activity, endomorphin 1 and 2 were similar to ATP, 100-fold less potent than isoproterenol, and 10,000-fold less potent than acetylcholine. These data demonstrate that endomorphin 1 and 2 have significant naloxone-sensitive vasodilator activity in the hindquarters vascular bed of the rat.
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PMID:The endogenous mu-opioid agonists, endomorphin 1 and 2, have vasodilator activity in the hindquarters vascular bed of the rat. 941 82

Intrathecal endomorphin-1 and endomorphin-2 (0.25-50 micrograms) dose-relatedly reduced all components of electrical evoked C-fibre responses of spinal neurones. These effects were partially reversed by naloxone. Endomorphin-1, but not endomorphin-2, dose-relatedly reduced the A beta-fibre evoked responses. Peak inhibitory effects of endomorphin-1 and -2 were at 15-20 min post-administration. Thus spinal endomorphin-2 had selective effects on noxious responses, whereas endomorphin-1 was non-selective.
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PMID:Distinct inhibitory effects of spinal endomorphin-1 and endomorphin-2 on evoked dorsal horn neuronal responses in the rat. 942 96

Endomorphin-1 (Tyr-Pro-Trp-Phe-NH2) and endomorphin-2 (Tyr-Pro-Phe-Phe-NH2) were previously isolated from bovine brain. Both peptides showed the greatest selectivity and affinity for the mu opiate receptor of any endogenous substance found to date and may serve as natural ligands for the mu-opiate receptor. We have purified them from the fronto-parietal cortex of human brain tissue by solid phase extraction and high performance liquid chromatography. Peptide content was followed by a specific and sensitive radioimmunoassay with an antibody that was generated against endomorphin-1. The isolated endomorphins showed full biological activity. The tetrapeptides were found in human brain in much higher amounts than in bovine frontal cortex.
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PMID:Isolation of relatively large amounts of endomorphin-1 and endomorphin-2 from human brain cortex. 943 27

Endomorphin-1 (Tyr-Pro-Trp-Phe-NH2) and endomorphin-2 (Tyr-Pro-Phe-Phe-NH2) are endogenous ligands that have greater affinity and selectivity for the mu-opiate receptor than any other known mammalian peptide. A polyclonal antiserum, screened for specificity to endomorphin-2 by immunodot-blot assay and preabsorption controls, was used for localization of this peptide. Immunocytochemistry performed on the brainstem, spinal cord, and sensory ganglia of rats by the avidin-biotin-peroxidase method revealed a continuous dense aggregation of endomorphin-2-like immunoreactive varicose fibers in the superficial laminae of the dorsal horn of the medulla and spinal cord. Immunoreactive fibers were detected in the dorsal root as well as within the dorsal root ganglia. The results suggest that endomorphin-2 is synthesized in primary sensory neurons in ganglia, transported to the superficial dorsal horn, and released near neurons expressing mu receptors. Its distribution appears to represent a functional unit likely to be associated with modulation of nociceptive stimuli.
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PMID:Localization of endomorphin-2-like immunoreactivity in the rat medulla and spinal cord. 943 28

The endogenous opioid peptides, endomorphin 1 and 2, are newly isolated, potent, and selective mu-opioid receptor agonists. In the present study, responses to endomorphin 1 and 2 were investigated in the systemic vascular bed of the rat. Endomorphin 1 and 2 induced dose-related decreases in systemic arterial pressure when injected in doses of 1-30 nmol/kg i.v. In terms of relative vasodepressor activity, endomorphin 1 and 2 were approximately equipotent with each other and with the ORL1 ligand, nociceptin (orphanin FQ), and were about 10-fold more potent than met-enkephalin in decreasing systemic arterial pressure. Vasodepressor responses to endomorphin 1 and 2 and met-enkephalin, but not to nociceptin, were inhibited by the opioid receptor antagonist, naloxone. These results demonstrate that endomorphin 1 and 2 produce significant naloxone-sensitive decreases in systemic arterial pressure.
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PMID:Endomorphin 1 and 2, endogenous mu-opioid agonists, decrease systemic arterial pressure in the rat. 951 3

Endomorphin-1 is a peptide whose binding selectivity suggests a role as an endogenous ligand at mu-opioid receptors. In the present study, the effect of endomorphin-1 on mu receptor-coupled G proteins was compared with that of the mu agonist DAMGO by using agonist-stimulated [35S]GTPgammaS binding in rat brain. [35S]GTPgammaS autoradiography revealed a similar localization of endomorphin-1- and DAMGO-stimulated [35S]GTPgammaS binding in areas including thalamus, caudate-putamen, amygdala, periaqueductal gray, parabrachial nucleus, and nucleus tractus solitarius. Naloxone blocked endomorphin-1-stimulated labeling in all regions examined. Although the distribution of endomorphin-1-stimulated [35S]GTPgammaS binding resembled that of DAMGO, the magnitude of endomorphin-1-stimulated binding was significantly lower than that produced by DAMGO. Concentration-effect curves of endomorphin-1 and DAMGO in thalamic membranes confirmed that endomorphin-1 produced only 70% of DAMGO-stimulated [35S]GTPgammaS binding. Differences in maximal stimulation of [35S]GTPgammaS binding between DAMGO and endomorphin-1 were magnified by increasing GDP concentrations, and saturation analysis of net endomorphin-1-stimulated [35S]GTPgammaS binding revealed a lower apparent Bmax value than that obtained with DAMGO. Endomorphin-1 also partially antagonized DAMGO stimulation of [35S]GTPgammaS binding. These results demonstrate that endomorphin-1 is a partial agonist for G protein activation at the mu-opioid receptor in brain.
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PMID:Endomorphin-stimulated [35S]GTPgammaS binding in rat brain: evidence for partial agonist activity at mu-opioid receptors. 952 74

Endomorphin-1 and -2, recently isolated endogenous peptides specific for the mu-opioid receptor, inhibited Ca2+ channel currents with EC50 of 6 and 9 nM, respectively, in NG108-15 cells transformed to express the cloned rat mu-opioid receptor. On the other hand, they elicited no response in nontransfected NG108-15 cells. It is concluded that endomorphin-1 and -2 induce Ca2+ channel inhibition by selectively activating the mu-opioid receptor.
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PMID:Ca2+ channel inhibition by endomorphins via the cloned mu-opioid receptor expressed in NG108-15 cells. 953 2

Endomorphin-1 and -2 are potent and selective agonists for the mu-opioid receptor which have recently been isolated from bovine brain extracts. In the present study we used polyclonal antibodies specific for endomorphin-2 to determine its immunocytochemical distribution in the rat brain and spinal cord Endomorphin-2-like immunoreactivity was confined to varicose fibers with an overall discrete distribution within the central nervous system. The immunostaining was completely abolished by preincubation of the antiserum with endomorphin-2 but not with endomorphin-1. Endomorphin-2-like immunoreactivity was enriched in many but not all brain regions known to contain dense mu-opioid receptors, including nucleus accumbens, septum, midline thalamic nuclei, hypothalamic and amygdala nuclei, locus coeruleus, periaqueductal gray and spinal cord dorsal horn. In contrast, endomorphin-2 was absent from the cortex, striatum, hippocampus, nucleus of the solitary tract and dorsal root ganglia. Dual-labeling experiments revealed that endomorphin-2-immunoreactive nerve fibers did not co-contain any other opioid peptide. Thus, the present findings strongly suggest that endomorphin-2 may be a natural ligand for the mu-opioid receptor likely to be involved in the modulation of nociceptive transmission and reward-seeking behavior.
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PMID:Immunofluorescent identification of endomorphin-2-containing nerve fibers and terminals in the rat brain and spinal cord. 960 62


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